Studies of the inner ear have been extended to the level of the single cells, and physiological studies, in particular, have advanced to the use of isolated inner ear living cells: i.e., outer hair cells (OHCs), inner hair cells (IHCs), Deiter's cells, and Hensen's cells. Here, we describe a rapid isolation technique for inner ear cells from the guinea-pig cochlea. Some proteolytic enzymes used for the isolation were found to affect the properties of the K currents in the isolated IHCs. While extracellular application of sodium salicylate induced an acute change in the shape of the isolated OHCs. Dexamethasone suppressed the salicylate-induced morphological changes of the cells. We describe the device used to perfuse the patch electrode for exchanging the intracellular medium of the isolated cells.
The purpose of this paper is to give an account of the vestibular nuclei from the point of view of phylogeny, behaviors, and neural networks of the vestibular nuclei. In the early vertebrates, the vestibular endorgans developed by isolation of the lateral line organ from the body surface. Although vestibular control based on inertial inputs works ideally under a stationary space, it breaks down in moving spaces. To compensate for the shortcoming, discomfort (motion sickness) was utilized to avoid moving spaces. Along with progress of locomotion, the vestibular cerebellum developed as a supplementary route of the vestibular nuclei to stabilize the gaze and posture; the flocculus for visual-inertial integration, and the uvula-nodulus for gravito-inertial integration. Further, the vestibular cerebellum (vermis) and the somatically arranged lateral vestibular nucleus developed for coordination of posture and four-limb locomotion. The superior vestibular nucleus is distributed centrally by the canal fibers and flocculus fibers of visual origin, and peripherally by the uvula-nodulus fibers of otolith origin. The nucleus carries spatial rotation with gravito-inertial axis to the ocular motor nuclei. Body balance is maintained by a somatic-to-spatial transformation of the coordinates, that is, transfer of contents of the cerebellum-fastigial-and-vestibular nuclues routes to the vestibular nucleus-motor nucleus routes. Thus, gaze and posture are stable when spatial coordinates remain still in space, but they become unstable when the coordinates are moving in space.
Posterior circulation disturbance, commonly known as vertebrobasilar insufficiency (VBI), is often associated with symptoms such as vertigo and instability. These various symptoms are thought to be due to hemodynamic disorders of the vertebrobasilar circulation that temporarily damage the vestibular nucleus (VN) and/or the cochlear nucleus (CN) within the brainstem. In this study, using a Laser-Doppler approach, we investigated the brainstem blood flow (BBF) feeding the vertebrobasilar system in order to estimate the influence of continuous intravenous infusion of prostaglandinE1 (PGE1), which acts as a microvascular dilator, in normal rats in this study. The following results were obtained. 1. During continuous intravenous infusion of PGE1 (at doses of 5 and 10ng/min/kg), no significant fluctuations of physiological parameters (PaO2, PaCO2, pH, saturation, body temperature, mean arterial blood pressure) were observed. However, the mean arterial blood pressure showed a tendency to decline after 45 minutes of continuous infusion of the higher dose (10ng/min/kg). 2. The BBF in the rats increased significantly to about 120% of the initial level after 30 minutes of continuous infusion of PGE1, compared to control infusion of saline. 3. Dose-dependent increases in the BBF were apparent after 60 minutes' continuous infusion. Considering the particular construction of the perforating vessels within the brainstem in both the VN and CN, the BBF measured in this investigation sensibly reflects is considered to reliably reflect the blood flow in these two nuclei. Therefore, we conclude that continuous intravenous infusion of PGE1 might be efficacious in cases of vertigo, equilibrium dysfunction and hearing impairment which directly result from circulation disturbances of the brainstem, because PGE1 would increase the blood flow to the VN and CN via improvement of the microvascular circulation within the brainstem.
Vertigo attacks with severe nausea and vomiting are frequently seen in emergency medical care. The present study was conducted to investigate whether bedside nystagmus observation might provide useful information for prediction of the clinical course during acute hospitalization and for determination of steroid administration in patients with peripheral vestibular disorders. We reviewed the electronystagmography (ENG) records of 38 patients with peripheral vestibular disorder who were hospitalized because of rotary vertigo, severe nausea, and/or vomiting. The patients were diagnosed as having acute peripheral vestibular disorder between January 2004 and February 2006 at the university hospital or its affiliates. Correlations between the withdrawal period duration of spontaneous nystagmus and the results of subsequent laboratory caloric testing by computerized ENG were examined. The 38 patients were divided into the short-decaying and long-lasting groups on the basis of the nystagmus duration. Half of the patients had the short-decaying type of nystagmus; their unidirectional spontaneous nystagmus disappeared within a few days. This group showed a female preponderance (male 2, female 17), recovered quickly from vertigo, and were out of bed within a few days. In contrast, the group with the long-lasting type of nystagmus showed no gender preponderance (male 9, female 10), and also a relatively high incidence of canal paresis on caloric testing (72.2%). Our results suggest that there are at least two types of peripheral vestibular disorders, which we designated as "benign paroxysmal spontaneous vertigo" and vestibular neuritis. We recognized the fact that daily short-time bedside observation of spontaneous nystagmus can provide prognostic information in patients with sudden vertigo at the very first visit. Steroid administration may be recommended when spontaneous nystagmus lasts more than 3 days, because vestibular neuritis would be strongly suspected in such cases.
The clinical features of 131 young patients (age<20 years) who were referred to our clinic for evaluation of balance problems were studied. The average age of the 131 patients was 13.7 years (4-19 years). The patients consisted of 66 males and 65 females. The population of patients increased with age in both males and females. Among the diagnoses were benign recurrent vertigo (BRV) in 15 cases (11%), psychogenic dizziness/vertigo in 14 cases (10%), Meniere's disease in 13 cases (9%), benign paroxysmal positional vertigo (BPPV) in 10 cases (8%), and orthostatic hypotension in 8 cases (6%). We noticed that BRV was the commonest cause of vertigo among the patients aged 10 years or younger. Some of our patients with BRV complained of aural fullness, tinnitus, nausea/vomiting and photophobia/phonophobia. While BRV is known to be one of the causes of episodic vertigo in children, probably a childhood manifestation of migraine, the lesion sites and pathophysiology of BRV remain unclear. Further study is required.
This study was conducted to investigate the factors influencing the walking speed in persons with intellectual disabilities (ID). The subjects were 181 persons with ID (male, 126; female, 55; 14 persons with autism; 22 with Down's Syndrome (DS)). The subjects were asked to walk on a straight 14-meter-long walkway with a flat floor at their preferred speed (PSW) and then at their maximum speed (MSW). They were asked to walk as fast as possible twice and the walk at the higher speed was designated as the MSW. The walking time in the middle of the walkway, 2 to 12 meters from the start, was measured by a stopwatch, to calculate the walking speed (m/sec). Stepwise multiple regression analysis was used. The dependent variables used were the PSW and the MSW, and the independent variables were the sex, age, height, weight, IQ, presence/absence of autism, and presence/absence of DS. The results were as follows: (1) The PSW was only related to the presence/absence of DS; persons with DS walked more slowly than persons with the other IDs. (2) The MSW was related to the IQ and the presence/absence of DS. Persons with higher IQ walked faster than those with a lower IQ, and persons with DS walked more slowly than persons with other IDs. These characteristics of the walking speed in persons with DS were discussed in terms of the motor dysfunction and compensatory strategies.
Introduction: The importance of the relationship between vertigo and headache, especially migraine, has been recognized. Vertigo has been found to be three times more common in patients with migraine than in controls, and migraine is found at a prevalence of 30%-50% in patients presenting with vertigo. Several authors have proposed different diagnostic criteria for defining migrainous vertigo and vestibular migraine. In this study, we attempted to clarify the current situation of migraine-related dizziness at our institute. Subjects and Methods: A retrospective review of 9 patients with migraine-related vertigo who visited our institute was conducted. We used the diagnostic criteria proposed by Neuhauser (2001). Results: Of the 9 patients, 1 was male and 8 were female; 6 patients had visited a neurosurgeon once, 3 patients had been diagnosed once as having Meniere's disease, although they had normal hearing. Calcium channel blockers, antidepressants, SSRIs (Selective Serotonin Reuptake Inhibitors) and anxiolytics had been prescribed as prophylactic agents. Of the 9 patients, 5 improved with the prophylactic treatment, 2 improved slightly, and 2 showed no change. The patients who showed improvement in the migraine with the prophylactic treatment also showed improvement of their vertigo at the same time. As acute-phase treatment NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) and triptans were prescribed. Three patients had a past history of BPPV (benign paroxysmal positional vertigo). Conclusion: The importance of diagnosis of migrane-associated vertigo was confirmed, since both prophylactic and acute-phase treatment were effective against both migraine and vertigo in these patients. To obtain further evidence for the treatment of migraine-associated vertigo, a more organized study should be conducted. The relationship between BPPV and migraine-associated vertigo should also be investigated in a future study.
From numerous clinical investigations and questionnaire surveys, I have obtained the following results regarding Meniere's disease. 1. Patients with Meniere's disease, as compared to the control population, differ little in lifestyles or daily anxieties, but possess significantly (p<0.01) stronger self-inhibition and engrossment. Meniere's disease may be caused by discontent with others' expression of gratitude or appraisal. 2. Low-tone sensorineural hearing loss, which resembles Meniere's disease except in not being associated with vertigo, is a milder form of Meniere's disease that occurs when the causative factors, both personal and environmental, are less severe or more transient. 3. Methods for prevention and therapy of Meniere's disease have been provided by our studies. Patients should be instructed (1) to understand the causative factors, (2) to decrease self-inhibition and not be concerned about others' expression of gratitude or appraisal, (3) to sleep well and to perform aerobic exercises, and (4) to enjoy chatting, singing or hobbies. 4. Long-lasting 60-dB hearing loss recovered to normal hearing in a 66-year-old patient with Meniere's disease after he performed aerobic exercises three times a week for several months. The results in this case suggest that the most important aspect in the treatment of Meniere's disease is increase of the local blood flow, which can be achieved by continuous aerobic exercises.
The genetics of Meniere's disease (MD), including the KCNE genes, COCH gene, and HLA genes, was reviewed and discussed. Single nucleotide polymorphisms (SNPs) in the KCNE genes might determine the susceptibility to MD. Variations in the HLA genes may also be related to the development of MD. To identify more genes that might possibly be closely related to the development of MD, gene profiling of human endolymphatic sac (ES) harvested from MD patients and vestibular schwannoma (VN) patients was performed using a DNA micro-array technique. Many up- and downregulated genes in the ES harvested from the MD patients were identified. The genes were classified into several subgroups according to their physiological functions. Some potassium channel genes, including Kir4.1, and several stress-related genes were significantly downregulated in the ES harvested from the MD patients. In future, genetic studies of MD will make it possible to determine more genes whose mutations/variations could lead to the development of MD, which would make possible the invention of a DNA-Chip for the diagnosis of MD. Such a DNA-Chip might be applied clinically to prevent MD, predict individual patients' prognosis and apply the most suitable treatment for individual patients.
We investigated and discussed the characteristics of blood circulation in the peripheral vestibular system by comparing that of cochleae. It was suggested that while embolic or thrombotic events occasionally occur in the vestibular end organs, they do not affect the cochleae. The vestibule, especially the saccule, has an environment which makes it vulnerable to hemodynamic transitional ischemia attacks (TIA) by the blood steal phenomenon. It has been assumed that the diagnostic criterion of VBI is assumed TIA in the vertebrobasilar artery area; however, a more peripheral site of the vestibular end organ also has an environment of TIA occurrence. Future treatment of inner ear disorders due to blood circulation disturbances should be performed according to the results of this study.
Patients with orthostatic dysregulation (OD)-associated disease may show autonomic disorders more frequently as compared with patients with other types of dizziness. However, the pathological mechanisms of OD remain unclear. We examined the cardiovascular autonomic function in dizzy patients with postural orthostatic tachycardia syndrome (POTS) or chronic orthostatic intolerance (OI) in order to evaluate the contribution of the autonomic disorders to the occurrence of dizziness. Heart rate variability analysis during the Schellong test showed that patients with POTS have hypo-parasympathetic function and relative hyper-sympathetic function, and that some patients with OI also have hypo-parasympathetic function. In our clinic, single therapy with a β1-blocker (Atenolol) for patients with POTS or single therapy with an a- agonist for patients with OI relieved orthostatic symptoms in 60% of the patients with POTS and OI. Further clinical studies on OD-associated disease to evaluate methods for accurate diagnosis and appropriate combined physical and pharmacotherapy may improve the outcomes in patients with OD-associated disease.
The hypothesis that certain types of vertigo develop through immunopathological mechanisms has been advocated for over 80 years. These days, many reports have been published that link immunity and vertigo with a variety of proposed immune-related etiologies, from autoimmunity to non-autoimmunity. Due to the inaccessibility of the labyrinth, it is difficult to take out obtain specimens of the inner ear tissue. In this paper, we present an animal model of Meniere's disease. Immune reaction following secondary antigen challenge in the endolymphatic sac of guinea pigs led to the development of endolymphatic hydrops, fluctuating hearing loss, precipitation of vertigo and suppression of the caloric response, similar to the symptomatology of Meniere's disease. These results strongly suggest that immune reaction in the endolymphatic sac is the likely cause of vertigo in Meniere's disesae. It is difficult to clinically distinguish between autoimmune inner ear disease and Meniere's disease, because of their clinical similarity. Western blotting examination of the serum for inner ear autoantibodies may aid in the differential diagnosis. Immunosuppressive drug treatment may be effective in patients with severe vertigo who show resistance to therapies used for Meniere's disease.
Based on our recent papers (Horii A et al. Otol Neurotol 2004, Horii A et al., J Vestibular Res 2007), we discussed the psychiatric involvement in patients with vertigo and dizziness. Seventy percent of patients with chronic dizziness showed a high score in the Hospital Anxiety and Depression Scale (HADS), suggesting that many dizzy patients have comorbid psychiatric disorders. Fluvoxamine, one of the selective serotonin reuptake inhibitors (SSRIs), administered at a dose of 200mg per day was effective for subjective handicaps due to dizziness in patients with or without neuro-otologic illnesses, owing to its actions on both the comorbid anxiety and depressive disorder. More aggressive psychiatric treatment, such as administration of higher doses, may be the next step of treatment for non-responders without neuro-otologic diseases, because these patients have been shown to suffer from more severe psychiatric illnesses. In contrast, other types of drugs that are known to help recovery of the vestibular function are recommended for neuro-otologic diseases in patients without clinically significant anxiety or depression and non-responders to fluvoxamine. The main causes of dizziness in patients without physical neuro-otologic findings were psychiatric disorders. Bidirectional relationships between vertigo/dizziness and psychiatric disorders could be explained by the anatomical connections between the brainstem and limbic system, including the amygdala.